Scopoletin Ameliorates Lipopolysaccharide Induced Neuroinflammation, Oxidative Stress and Cognitive Dysfunction in Mice: A Mechanistic Study

Background: Alzheimer’s disease (AD), a progressive neuropsychiatric disorder, is characterized by neuroinflammation, β-amyloid plaques and neurofibrillary tangles. It has been demonstrated that systemic inflammation and neuroinflammation caused by lipopolysaccharide (LPS) injections in rodents leads to elevation in Aβ levels and neuronal cell death, finally resulting in cognitive impairment.

Methods: Animals received the experimental compound – Scopoletin (2.5, 5 or 10 mg/kg, i.p) for 31 days. Initially for 14 days, they received only the experimental drug; thereafter for the next 7 days they received LPS (0.25 mg/kg i.p) along with the experimental molecules.

Treatment with the experimental molecules was continued for the next 10 days and behavioural tests were performed. Animals were sacrificed on day 32 and biochemical tests were performed on brain tissue homogenate.

Results: Scopoletin administration improved memory and cognition as indicated by reduction of escape latency in Morris water maze test and increased number of entries in Y maze test. Malondialdehyde was significantly increased after LPS administration and reduced glutathione, catalyse and superoxide dismutase were significantly reduced in mice brains. Treatment with scopoletin significantly reduced oxidative stress. Inflammatory markers. β-secretase and apoptotic markers were also markedly reduced.

Conclusion: At medium and high dose, Scopoletin showed promise response as a prophylactic entity in the LPS induced neuroinflamation and cognitive dysfunction model in mice.